The present invention relates to novel treatments for infectious diseases, in particular, an occlusive dressing and methods of treatment.
Occurring worldwide, most fungi are largely invisible to the naked eye, living for the most part in soil, dead matter, and as symbions of plants, animals, or other fungi. However, several species of the fungi are significant pathogens of humans and other animals or crops. The most commonly known human pathogens are part of the Candida, Aspergillus and/or Fusarium species.
Candida albicans is among the gut flora, the many organisms which live in the human mouth and gastrointestinal tract. Under normal circumstances, C. albicans lives in 80% of the human population with no harmful effects, although overgrowth results in candidiasis. Candida albicans is a causal agent of opportunistic oral and genital infections in humans. Systemic fungal infections have emerged as important causes of morbidity and mortality in immunocompromised patients (e.g., AIDS, cancer chemotherapy, organ or bone marrow transplantation). In addition, hospital-related infections in patients not previously considered at risk (e.g. patients in an intensive care unit) have become a cause of major health concern.
Today, there are 4 classes of established antifungal drugs on the market: (1) the polyenes (e.g. amphotericin B, nystatin, natamycin), (2) the azoles (e.g. fluconazole, itraconazole, voriconazole), (3) allylamines (e.g. terbinafine), and (4) the newly introduced echinocandins (e.g. caspofungin). Of these classes, only the polyenes, azoles and echinocandins are used to treat systemic fungal infections, not the allylamines. All the currently marketed antifungal drugs have major drawbacks, including no broad-spectrum activity, no per oral absorption, side-effects, low antifungal activity, no fungicidal activity, drug-drug interactions and high costs.
Diseases in other areas, such as Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) and resistant bacteria such as Methacillin-resistant Staphylococcal aureus (MRSA) and Staphylococcal epidermidis (MRSE), have created multiple problems for pregnancy and intimate relationships. Furthermore, animal husbandry indicates that diseases will reduce the yield of animals for prized animals which could be devastating to limited breeding cycles in certain species.
Current delivery systems lack the ability to create high surface area contact points; therefore, recurring disease, infection and reinfections are prevalent. This rate increases for individuals with compromised immunes systems, such as those with cancer and HIV, for individuals with multiple partners or conditions that can lead to reinfection.
By utilizing the unique elastomeric matrix described herein, the end user would have increased contact areas with an extremely thin film of drug in the delivery device, thereby alerting the environment for recurring infectious diseases, preventing spread of disease and in many cases effectuating a cure by breaking the cycle of spread of disease.
There is still a stringent need in the art for potent antifungals, antibacterial and antivirals for topical or systemic infections, especially with a broad spectrum activity against multiple species, and which can readily transmit into the multiple dermal layers via creating a high surface area of contact points and thereby bring individuals to a cure.
Therefore a goal of the present invention is to satisfy this urgent need by identifying efficient and non-harmful pharmaceutically active ingredients and combinations of ingredients for the prevention and treatment of infectious diseases, especially of fungal, bacterial, viral infections and other dermal wounds and abrasions in animals and in humans.
WO 2010/003197 relates to compounds that are substituted morpholin-2-one structure and it has been shown in the present invention that they possess antifungal activity for treatment of fungal diseases, but does not utilize the delivery system of this invention, instead using polymer carriers such as for example polyesters, polyamino acids, polyvinyl pyrrolidone, ethylene-vinyl acetate copolymers, methylcellulose, carboxymethylcellulose, protamine sulfate, but not SEBS and SEPS.
U.S. Pat. Nos. 5,466,235; 5,782,818; 5,806,523; and 5,807,360 relate to a polymer which does not demonstrate application for dermal use for the delivery of medications which are anti-fungal, ant-bacterial or anti-viral.
WO 2007/141513 provides coumarin compounds, in particular glycosidic coumarin compounds, useful in the treatment of dermatophyte fungal infections.
EP 1 212 093 describes Emu Oil, an animal-derived lipid that is useful as a carrying agent for anti-microbial formulations, that are disclosed as useful components in anti-bacterial, anti-fungal, and anti-viral treatments.
Transdermal Delivery
Percutaneous or transdermal delivery of pharmacologically active agents has become feasible in recent years largely due to vehicles therefore which allow increased permeation of said agents into the body surface to which applied. Such agents which may be useful for the preparation of a xanomeline transdermal patch formulation include, but are not necessarily limited to, dimethylsulfoxide (U.S. Pat. No. 3,551,554); various 1-substituted azacycloalkan-2-ones such as azone (U.S. Pat. Nos. 4,562,075, 4,405,616, 4,326,893 and 3,989,816); sugar esters in combination with sulfoxide or phosphine oxide (U.S. Pat. Nos. 4,130,667, 4,130,643, 4,046,886, 3,952,099, and 3,896,238); lower alkyl amides (U.S. Pat. No. 3,472,931); certain aliphatic sulfoxides (U.S. Pat. No. 3,903,256); a composition containing glycerol monooleate, ethanol and isopropyl myristate (U.S. Pat. No. 4,335,115); a binary mixture of 1-dodecylazacycloheptan-2-one and a compound selected from a diol or a second N-substituted azacycloalkyl-2-one (U.S. Pat. No. 4,557,934); and polyethylene glycol monolaurate (U.S. Pat. No. 4,568,343).
A variety of devices for transdermal delivery including gelling agents, cream and ointment bases, and the like, have been described in the art. For example, such devices include, but are not limited to those described in U.S. Pat. Nos. 3,598,122, 3,598,123, 3,710,795, 3,731,683, 3,742,951, 3,814,097, 3,921,636, 3,972,995, 3,993,072, 3,993,073, 3,996,934, 4,031,894, 4,060,084, 4,069,307, 4,077,407, 4,201,211, 4,230,105, 4,292,299, and 4,292,303.
U.S. Pat. Nos. 3,598,122 and 3,598,123 describe silicone rubbers and hydrophilic polymers of monoesters of an olefinic acid, such as acrylic acid and methacrylic acid. Exemplary polymers of this class include poly (hydroxyethylacrylate) and poly (hydroxyethylmethacrylate).
U.S. Pat. Nos. 3,710,795, 3,731,683 and 3,742,951 describe a solid inner matrix material having drug dispersed there through surrounded by an outer polymeric membrane which includes heat shrinkable polymeric films in the form of tubes, spheres, ellipsoids, envelopes, etc.
U.S. Pat. No. 3,814,097 is a pad provided with tiny spikes. These tiny spikes augment the absorption of the drug.
U.S. Pat. No. 3,921,636 is a device which comprises a plurality of reservoirs containing drug distributed through a matrix. Especially, the invention relates to an intrauterine drug delivery device comprising a matrix of silicone elastomer having a plurality of drug reservoirs dispersed therethrough, the reservoirs comprising progesterone particles each microencapsulated within a drug release rate controlling polyethylene wall. Suitable materials permeable to the passage of drug include copolymers such as acrylonitrile/dithioglycidol, acrylonitrile/ethylene oxide, poly(vinyl butyral) comprised of 11 to 45% free hydroxyls, anisotropic permeable microporous membranes of ionically associated polyelectrolytes, the polymers formed by the coprecipitation of a polycation and a polyanion, treated aliphatic polyamides and the like; natural gums such as guar, acacia, pectins, and the like. Also, materials such as starch, regenerated cellulose, cellulose diacetate, cellulose triacetate, regenerated proteins, polyurethanes, polydinitrites, polyarylenes, and polycarbonates are disclosed.
U.S. Pat. No. 3,972,995 relates to a buccal dossage form comprising a moisture-activated adhesive precursor comprised of a hydrocolloid admixed with polyvinylpyrrolidone, water-insoluble support member comprised of a film of ethylcellulose plasticized with castor oil as well as a moisture activated adhesive precursor comprised of finely powdered Karaya gum in a viscous solution of polyvinylpyrrolidone in polyethylene glycol.
U.S. Pat. Nos. 3,996,934, 3,996,934 is a bandage comprised of a laminate of a backing member defining one face surface of a bandage and a middle reservoir containing a drug.
U.S. Pat. Nos. 4,031,894, 4,060,084, 4,060,084 and 4,201,211 is a bandage that is a four-layer laminate of a protective backing; a gelled, mineral oil-polyisobutene-scopolamine reservoir lamina that is the source of the constant dosage; a microporous membrane that controls the constant dosage rate; and a gelled, mineral oil-polyisobutene-drug adhesive layer that is the source of the pulse dose and the means by which the bandage is attached to the skin.
U.S. Pat. No. 4,069,307 is a drug-delivery device for releasing a drug at a continuous and controlled rate for a prolonged period of time is comprised of a shaped body of polymeric material containing a pharmaceutically acceptable drug and permeable to passage of the drug by diffusion. The polymeric material is an ethylene-vinyl acetate copolymer having a vinyl acetate content of about 4 to 80% by weight and a melt index of about 0.1 to 1000 grams per 10 minutes.
U.S. Pat. No. 4,077,407 relates to osmotic device for delivering an active agent which contains polymeric cellulose esters and copolymeric cellulose esters such as mono, di, and tricellulose acylates.
U.S. Pat. No. 4,230,105 is a pressure sensitive adhesive composition comprising hexane, polyvinylethylether, polyvinylethyl ether, glycerol ester of hydrogenated rosin and polyethylene glycol 400.
U.S. Pat. No. 4,292,299 relates to a slow-releasing medical preparation to be administered by adhering to a wet mucous surface, wherein the polymer of the adhesive layer is at least one polymer selected from a group comprising acrylic acids or their pharmaceutically acceptable nontoxic salts, copolymers of acrylic acid or their pharmaceutically acceptable nontoxic salts, hydrophilic vinyl copolymers not copolymerized with acrylic acid as a main component, hydrophilic cellulose derivatives, polysaccharides or their derivatives and gelatine or collagen or their derivatives with improved swellability. The polymer of the adhesive layer is a mixture of cellulose ether and polyacrylic acid (or its salt) or copolymer of acrylic acid (or its salt). The cellulose ether is methyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose or their mixture.
U.S. Pat. No. 4,292,303 is a transdermal delivery system of clonidine in a matrix comprising a polar plasticizer, such as polyethylene glycol, or a mixture of glycerol and polyethylene glycol, and with polyvinylalcohol and a water-soluble polymer such as an agar, gum arabic, gum tragacanth, polyacrylic acid, polymethacrylic acid, polyvinyloxazolidone, polyvinylmorpholinone, and polyvinylpiperidonepolyvinylpyrrolidone. Polyalkylene glycols such as polyethylene glycol and polypropylene glycol may replace all or part of the glycerol.
US 2009-0028929 describes a transdermal patch containing nitroglycerine and a matrix layer comprising: nitroglycerin, acrylic acid/2-ethyl-acrylate/methyl-acrylate copolymer, sorbitan monooleate, propylene glycol and optionally excipients.
WO 1996/023463 relates to a transdermal patch for treating Alzheimers Disease containing xanomeline, azone, ethanol, water, propylene glycol, and gelling agent, such as Klucel HF.
There is a need for a composition which provides higher dermis concentrations of active agents and would therefore increase its therapeutic benefits in the treatment of skin conditions. The embodiments of this invention provide an improvement over traditional patches and topical products utilized to deliver medications.